Abstract

Objectives Rheumatoid arthritis (RA) is associated with an increased Epstein–Barr virus (EBV) blood DNA load, a robust immune response
to EBV and cross-reactive circulating antibodies to viral and self-antigens. However, the role of EBV in RA pathogenesis remains
elusive. Here, we investigated the relationship between synovial EBV infection, ectopic lymphoid structures (ELS) and immunity
to citrullinated self and EBV proteins.

Methods Latent and lytic EBV infection was investigated in 43 RA synovial tissues characterised for presence/absence of ELS and in
11 control osteoarthritis synovia using RT-PCR, in situ hybridisation and immunohistochemistry. Synovial production of anti-citrullinated
protein (ACPA) and anti-citrullinated EBV peptide (VCP1/VCP2) antibodies was investigated in situ and in vivo in the severe
combined immunodeficiency (SCID)/RA chimeric model.